Pyranone carboxamides

ABSTRACT

Pyranone carboxamides, e.g., 2,6-diphenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide, are prepared by cyclizing and dehydrogenating 2-aminomethylene-5-hydroxy-N-methyl-3-oxo-alkylamides and are useful as anti-allergic agents.

This invention relates to 4-oxo-pyrancarboxamide derivatives. Inparticular, this invention relates to alkyl and aryl substituted4-oxo-4H-pyran-3-carboxamides, processes, and intermediates used intheir preparation and their use in pharmaceutical compositions.

The compounds of this invention may be represented by the followingstructural formula: ##STR1## where R₁ and R₂ each independently is loweralkyl, i.e., alkyl having 1 to 4 carbon atoms, e.g., methyl, ethyl,isopropyl, and the like or ##STR2## where R₄ is hydrogen, halogen havingan atomic weight of from 19 to 36, lower alkoxy, i.e., alkoxy having 1to 4 carbon atoms, e.g., methoxy, ethoxy, and the like or lower alkyl asdefined above and

R₃ is lower alkyl as defined above.

The compounds of formula (I) may be prepared in accordance with thefollowing reaction scheme: ##STR3## where R₁, R₂, and R₃ are as definedabove.

The compounds of formula (I) are prepared by dehydrogenating a compoundof the formula (II) in an inert solvent in the presence ofdehydrogenating agent. The dehydrogenating agent can be any of thestandard dehydrogenating agents, such as sulfur ordichlorodicyanoquinone, the latter being especially preferred. Althoughthe particular inert solvent employed is not critical, it is preferredthat the reaction be carried out in an inert solvent such as thearomatic hydrocarbons, e.g., benzene, toluene, and the like, especiallybenzene, or halogenated hydrocarbons, e.g., ethylene dichloride,dichlorobenzene, and the like. The temperature at which the reaction iscarried out is not critical, but it is preferred that the reaction berun between about 50° C. to 180° C., preferably between about 80° C. to120° C. The time of the reaction also is not critical, but it ispreferred that the reaction be run for 5 to 24 hours, especially 16 to20 hours. The compounds of formula (I) are isolated by conventionaltechniques, e.g., extraction and evaporation.

The compounds of formula (II) may be prepared in accordance with thefollowing reaction scheme: ##STR4## where R₁, R₂, and R₃ are as definedabove.

The compounds of formula (II) are prepared by cyclizing a compound ofthe formula (III) with mineral acid in an inert solvent. The mineralacid can be concentrated or dilute hydrochloric acid, sulfuric acid,phosphoric acid, and the like, preferably concentrated hydrochloricacid. The inert solvent employed can be any solvent inert under thereaction conditions; but the lower alcohols having 1 to 4 carbons atoms,water, or mixtures thereof are preferred, especially ethyl alcohol. Thetemperature at which the reaction is carried out is not critical but itis preferred that the reaction be run between about 20° C. to 100° C.,preferably between about 25° C. to 30° C. The time of the reaction alsois not critical, but it is preferred that the reaction be run for 1 to 5hours, especially 1.5 to 3.5 hours. The compounds of formula (II) areisolated by conventional techniques, e.g., filtration andcrystallization.

The compound of formula (III) may be prepared in accordance with thefollowing reaction scheme: ##STR5## where R₁, R₂, and R₃ are as definedabove.

The compounds of formula (III) are prepared by hydrogenating a compoundof the formula (IV) with hydrogen in an inert solvent in the presence ofa hydrogenation catalyst. The hydrogenation catalyst can be any of thestandard hydrogenation catalysts, such as palladium on carbon, platinumoxide, Raney nickel, and the like, but 10 percent palladium on carbon isespecially preferred. Although the particular inert solvent used is notcritical, it is preferred that the reaction be carried out in solvents,such as the lower alkanols of 1 to 4 carbon atoms, dioxane,tetrahydrofuran, water, or mixtures of the above, especially ethanol.The temperature at which the reaction is carried out is also notcritical, but it is preferred that the reaction be run between about 20°C. to 100° C., preferably between about 25° C. to 30° C., especiallyroom temperature. The time of the reaction is not critical also, but itis preferred that the reaction be run for 1 to 18 hours, in particular,for the period of time required to absorb one equivalent of hydrogen.The compound of formula (III) is isolated by conventional techniques,e.g., filtration and evaporation.

The compounds of formula (IV) may be prepared according to the followingreaction scheme: ##STR6## where R₁, R₂, and R₃ are as defined above.

The compounds of formula (IV) are prepared by treating a compound of theformula (V) with a compound of the formula (VI) in the presence of aninert organic solvent. Although the particular solvent employed is notcritical, the preferred solvents include ethers, such as diethylether ortetrahydrofuran or an aliphatic hydrocarbon, such as pentane, hexane,heptane, and the like, preferably tetrahydrofuran. The temperature ofthe reaction is not critical, but it is preferred that the reaction berun at a temperature of from about -75° C. to -55° C., preferably fromabout -65° C. to -60° C. The reaction is run from about 1 to 5 hours,preferably from about 2.5 to 3.5 hours. The product is recovered usingconventional techniques, e.g., trituration followed by filtration.

The compounds of formula (V) may be prepared according to the followingreaction scheme: ##STR7## where R₄ is lower alkyl having 1 to 4 carbonatoms, and R₂ and R₃ are as defined above.

The compounds of formula (V) are prepared by treating a compound of theformula (VII) with a compound of the formula (VIII) in the presence ofan inert organic solvent. Although the particular solvent employed isnot critical, the preferred solvents include an ether such asdiethylether or tetrahydrofuran or an aliphatic hydrocarbon such aspentane, hexane, heptane, and the like, preferably hexane. Thetemperature of the reaction is not critical, but it is preferred thatthe reaction be run at a temperature of from about -75° C. to -55° C.,preferably from about -65° C. to -60° C. The reaction is run from about1 to 5 hours, preferably from about 2.5 to 3.5 hours. The compound offormula (V) is not isolated but employed in situ as a starting materialin the preparation of the compounds of formula (IV).

Many of the compounds of formulae (VI), (VII), and (VIII) are known andmay be prepared by methods described in the literature. The compounds offormulae (VI), (VII), and (VIII) not specifically described may beprepared by analogous methods from known starting materials.

The compounds of the formula (I) are also useful in the treatment ofallergic conditions, such as allergic asthma, as indicated by theirhistamine-release inhibiting activity in the passive cutaneousanaphylaxis test in the rat. Female rats (180 - 200 grams) aresensitized by intramuscular administration of 2 milligrams of eggalbumin (Merck Nr. 967) dissolved in 0.1 milliliters of physiologicalsaline and 0.5 milliliters of Haemophiluspertussis vaccine(Schweizerisches Serum and Impfinstitut, Bern; Nr. 115 325; 4 × 10¹⁰organism/milliliter) intraperitoneally. Fourteen days later, the animalsare exsanguinated, the blood centrifuged, the serum collected and deepfrozen. The serum thus obtained (anti-serum) is injected intradermally(0.1 milliliters of a 1:2 diluted serum per injection site) at foursites on the backs of untreated, female rats. Twenty-four hours later,each rat is administered 32 milligrams/kilogram of the test compound,intraperitoneally or orally as a suspension in tragacanth; and either 5or 30 minutes afterwards, in the case of intraperitoneal administration,or 60 minutes afterwards, in the case of oral administration, eggalbumin (5 milligrams/kilogram i.v.) dissolved in physiological salinecontaining 0.25 percent Evans Blue Dye (Merck Nr. 3169) is administered.The egg albumin elicits a cutaneous anaphylactic reaction, the intensityof which is proportional to the extent to which the Evans Blue Dyediffuses into the tissue surrounding each of the four sensitizationsites. Thirty minutes after the administration of the egg albumin, therats are killed with ether, the underside of the skin of the back ofeach animal is exposed and the diameter of the areas of blue dyesurrounding each of the four sensitization sites are measured. Each doseof the test compound is investigated in between four and six rats andthe mean diameter compared with the mean value obtained in foursolvent-treated control rats. The percentage inhibition is taken as thepercentage of the mean diameter in the test animals relative to the meandiameter in the controls.

For the above-mentioned use as anti-allergic agents, the dosageadministered will, of course, vary depending on the compound employed,mode of administration and treatment desired. However, in general,satisfactory results are obtained upon administration at a daily dosageof from about 0.1 to 50 milligrams/kilogram of animal body weight,conveniently given in divided doses two to four times daily, or insustained release form. For the larger mammals, the total daily dosageis in the range of from about 10 to 400 milligrams, and dosage formssuitable for oral administration comprise from about 2.5 to 200milligrams of the compound admixed with a solid or liquid pharmaceuticalcarrier or diluent.

Tablets and capsules containing the ingredients indicated below may beprepared by conventional techniques and are useful in the treatment ofallergy at a dose of one or two tablets just before bedtime.

    ______________________________________                                                           Weight (mg.)                                               Ingredients          Tablet    Capsule                                        ______________________________________                                        2,6-diphenyl-N-methyl-4-oxo-4H-                                               pyran-3-carboxamide  100       100                                            tragacanth           10        --                                             lactose              147.5     200                                            corn starch          25        --                                             talcum               15        --                                             magnesium stearate   2.5       --                                             Total                300 mg.   300 mg.                                        ______________________________________                                    

EXAMPLE 13-phenyl-5-(β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide

A suspension of 75 grams (0.348 mole) of3-phenyl-5,N-dimethyl-isoxazole-4-carboxamide in 1 liter oftetrahydrofuran is cooled to -65° C. and 478 milliliters of 1.6Mn-butyllithium in hexane (0.765 mole) is added dropwise maintaining thetemperature between -60° C. and -70° C. After the addition is complete,the orange suspension is stirred for 11/2 hours at -60° C. to -70° C.,and then 37.2 grams (0.350 mole) of benzaldehyde in 375 milliliterstetrahydrofuran is added dropwise maintaining the temperature between-60° C. and -70° C. After addition is complete, the mixture is stirred11/2 hours at -60° C. to -70° C. and then warmed to -30° C. and quenchedby the addition of saturated ammonium chloride solution. The mixture isfurther diluted with tetrahydrofuran and the layers are separated. Thetetrahydrofuran layer is washed twice with 50 percent brine, and oncewith brine, dried over anhydrous magnesium sulfate, filtered andevaporated in vacuo. The solid residue is triturated with a 50:50mixture of ether:petroleum ether, filtered and washed with cold ether togive 3-phenyl-5-(β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,m.p. 183° - 184° C.

Following the above procedure and using in place of3-phenyl-5,N-dimethyl-isoxazole-4-carboxamide, an equivalent amount of

a. 3-(p-chlorophenyl)-5,N-dimethyl-isoxazole-4-carboxamide,

b. 3-(p-fluorophenyl)-5,N-dimethyl-isoxazole-4-carboxamide,

c. 3-(p-tolyl)-5,N-dimethyl-isoxazole-4-carboxamide,

d. 3-(p-anisyl)-5,N-dimethyl-isoxazole-4-carboxamide, or

e. 3-ethyl-5,N-dimethyl-isoxazole-4-carboxamide,

there is obtained

a.3-(p-chlorophenyl)-5-(β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,

b.3-(p-fluorophenyl)-5-(β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,

c. 3-(p-tolyl)-5-(β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,

d. 3-(p-anisyl)-5-(β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,or

e. 3-ethyl-5-(βhydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,respectively.

Again following the same procedure and using in place of benzaldehyde anequivalent amount of

f. p-chlorobenzaldehyde,

g. p-fluorobenzaldehyde,

h. p-tolualdehyde,

i. p-anisaldehyde, or

j. pivalaldehyde,

there is obtained

f.3-phenyl-5-(4-chloro-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,

g.3-phenyl-5-(4-fluoro-βhydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,

h.3-phenyl-5-(4-methyl-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,

i.3-phenyl-5-(4-methoxy-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,or

j.3-phenyl-5-(3,3-dimethyl-2-hydroxybutyl)-N-methyl-isoxazole-4-carboxamide,respectively.

Again following the above procedure and using in place of3-phenyl-5,N-dimethyl-isoxazole-4-carboxamide an equivalent amount of3-ethyl-5,N-dimethyl-isoxazole-4-carboxamide and in place ofbenzaldehyde an equivalent amount of pivaldehyde there is obtained

k.3-ethyl-5-(3,3-dimethyl-2-hydroxybutyl)-N-methyl-isoxazole-4-carboxamide.

EXAMPLE 2 2-(α-aminobenzylidene)-5-hydroxy-N-methyl-3-oxo-5-phenylvaleramide

A mixture of 30.0 grams (0.093 mole) of3-phenyl-5-(β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide, 600milliliters of ethanol and 3.0 grams of 10 percent Palladium on carbonin hydrogenated at 50 p.s.i. until 1 equivalent of hydrogen is absorbed(about 5 hours). The mixture is filtered and the filtrate evaporated invacuo. The residue is then crystallized from methylene chloridepetroleum ether to give2-(α-aminobenzylidene)-5-hydroxy-N-methyl-3-oxo-5-phenylvaleramide, m.p.72° C. - 76° C.

Following the above procedure and using in place of3-phenyl-5-(β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide, anequivalent amount of

a.3-(p-chlorophenyl)-5-(β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,

b.3-(p-fluorophenyl)-5-(β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,

c. 3-(p-tolyl)-5-(β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,

d. 3-(p-anisyl)-5-(β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,

e. 3-ethyl-5-(β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,

f.3-phenyl-5-(4-chloro-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,

g.3-phenyl-5-(4-fluoro-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,

h.3-phenyl-5-(4-methyl-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,

i.3-phenyl-5-(4-methoxy-β-hydroxyphenethyl)-N-methyl-isoxazole-4-carboxamide,

j.3-phenyl-5-(3,3-dimethyl-2-hydroxybutyl)-N-methyl-isoxazole-4-carboxamide,or

k.3-ethyl-5-(3,3-dimethyl-2-hydroxybutyl)-N-methyl-isoxazole-4-carboxamide,

there is obtained

a.2-(α-amino-[p-chlorobenzylidene])-5-hydroxy-N-methyl-3-oxo-5-phenylvaleramide,

b.2-(α-amino-[p-fluorobenzylidene])-5-hydroxy-N-methyl-3-oxo-5-phenylvaleramide,

c.2-(α-amino-[p-methylbenzylidene])-5-hydroxy-N-methyl-3-oxo-5-phenylvaleramide,

d.2-(α-amino-[p-methoxybenzylidene])-5-hydroxy-N-methyl-3-oxo-5-phenylvaleramide,

e. 2-(α-aminopropylidene)-5-hydroxy-N-methyl-3-oxo-5-phenylvaleramide,

f.2-(αaminobenzylidene)-5-hydroxy-N-methyl-3-oxo-5-(p-chlorophenyl)-valeramide,

g.2-(α-aminobenzylidene)-5-hydroxy-N-methyl-3-oxo-5-(p-fluorophenyl)-valeramide,

h.2-(α-aminobenzylidene)-5-hydroxy-N-methyl-3-oxo-5-(p-tolyl)-valeramide,

i. 2-(α-aminobenzylidene)-5-hydroxy-N-methyl-3-oxo-5-(p-anisyl)valeramide,

j. 2-(α-aminobenzylidene)-5-hydroxy-6,6-N-trimethyl-3-oxo-heptanamide,or

k.2-(α-aminopropylidene)-5-hydroxy-6,6-N-trimethyl-3-oxo-heptanamide,respectively.

EXAMPLE 3 5,6-dihydro-2,6-diphenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide

A solution of 21.4 grams (0.066 mole) of2-(α-aminobenzylidene)-5-hydroxy-N-methyl-3-oxo-5-phenylvaleramide in220 milliliters of ethanol is treated by dropwise addition with 10milliliters of concentrated hydrochloric acid. The resulting suspensionis stirred for 1.5 hours at room temperature. Ether is then added, andthe mixture is filtered. The resulting solid is triturated thoroughlywith hot methanol to give5,6-dihydro-2,6-diphenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide, m.p.212° C. - 214° C.

Following the above procedure, but using in place of the2-(α-aminobenzylidene)-5-hydroxy-N-methyl-3-oxo-5-phenylvaleramide anequivalent amount of

a.2-(α-amino-[p-chlorobenzylidene])-5-hydroxy-N-methyl-3-oxo-5-phenylvaleramide,

b.2-(α-amino-[p-fluorobenzylidene])-5-hydroxy-N-methyl-3-oxo-5-phenylvaleramide,

c.2-(α-amino-[p-methylbenzylidene])-5-hydroxy-N-methyl-3-oxo-5-phenylvaleramide,

d.2-(α-amino-[p-methoxybenzylidene])-5-hydroxy-N-methyl-3-oxo-5-phenylvaleramide,

e. 2-(α-aminopropylidene])-5-hydroxy-N-methyl-3-oxo-5-phenylvaleramide,

f.2-(α-aminobenzylidene)-5-hydroxy-N-methyl-3-oxo-5-(p-chlorophenyl)-valeramide,

g.2-(α-aminobenzylidene)-5-hydroxy-N-methyl-3-oxo-5-(p-fluorophenyl)-valeramide,

h.2-(α-aminobenzylidene)-5-hydroxy-N-methyl-3-oxo-5-(p-tolyl)-valeramide,

i.2-(α-aminobenzylidene)-5-hydroxy-N-methyl-3-oxo-5-(p-anisyl)-valeramide,or

j. 2-(α-aminobenzylidene)-5-hydroxy-6,6-N-trimethyl-3-oxo-heptanamide,or

k. 2-(α-aminopropylidene)-5-hydroxy-6,6-N-trimethyl-3-oxo-heptanamide,

there is obtained

a.5,6-dihydro-2-(p-chlorophenyl)-6-phenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide,

b.5,6-dihydro-2-(p-fluorophenyl)-6-phenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide,

c.5,6-dihydro-2-(p-tolyl)-6-phenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide,

d.5,6-dihydro-2-(p-anisyl)-6-phenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide,

e. 5,6-dihydro-2-ethyl-6-phenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide,

f.5,6-dihydro-2-phenyl-6-(p-chlorophenyl)-N-methyl-4-oxo-4H-pyran-3-carboxamide,

g.5,6-dihydro-2-phenyl-6-(p-fluorophenyl)-N-methyl-4-oxo-4H-pyran-3-carboxamide,

h.5,6-dihydro-2-phenyl-6-(p-tolyl)-N-methyl-4-oxo-4H-pyran-3-carboxamide,

i.5,6-dihydro-2-phenyl-6-(p-anisyl)-N-methyl-4-oxo-4H-pyran-3-carboxamide,

j.5,6-dihydro-2-phenyl-6-(t-butyl)-N-methyl-4-oxo-4H-pyran-3-carboxamide,or

k.5,6-dihydro-2-ethyl-6-(t-butyl)-N-methyl-4-oxo-4H-pyran-3-carboxamide,respectively.

EXAMPLE 4 2,6-diphenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide

A mixture of 10.0 grams (0.0324 mole) of5,6-dihydro-2,6-diphenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide, 11.0grams (0.0485 mole) of dichloro dicyanoquinone and 200 milliliters ofbenzene is refluxed for 18 hours. The mixture is cooled and theprecipitate filtered and washed with benzene and methylenedichloride.The filtrate is evaporated to dryness and the residue is partitionedbetween methylenedichloride and 2N sodium hydroxide and the layersseparated. The organic layer is washed with 2N sodium hydroxide, waterand 50 percent brine, dried over magnesium sulfate, filtered andevaporated in vacuo. The residue is dissolved in a hot 50:50 mixture ofethanol:methanol, treated with decolorizing charcoal, filtered andevaporated in vacuo. The residue is crystallized from ethanol to give2,6-diphenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide, m.p. 196° C. - 197°C.

When the above procedure is carried out using in place of the5,6-dihydro-2,6-diphenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide anequivalent amount of

a.5,6-dihydro-2-(p-chlorophenyl)-6-phenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide,

b.5,6-dihydro-2-(p-fluorophenyl)-6-phenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide,

c.5,6-dihydro-2-(p-tolyl)-6-phenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide,

d.5,6-dihydro-2-(p-anisyl)-6-phenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide,

e. 5,6-dihydro-2-ethyl-6-phenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide,

f.5,6-dihydro-2-phenyl-6-(p-chlorophenyl)-N-methyl-4-oxo-4H-pyran-3-carboxamide,

g.5,6-dihydro-2-phenyl-6-(p-fluorophenyl)-N-methyl-4-oxo-4H-pyran-3-carboxamide,

h.5,6-dihydro-2-phenyl-6-(p-tolyl)-N-methyl-4-oxo-4H-pyran-3-carboxamide,

i.5,6-dihydro-2-phenyl-6-(p-anisyl)-N-methyl-4-oxo-4H-pyran-3-carboxamide,

j.5,6-dihydro-2-phenyl-6-(t-butyl)-N-methyl-4-oxo-4H-pyran-3-carboxamide,or

k.5,6-dihydro-2-ethyl-6-(t-butyl)-N-methyl-4-oxo-4H-pyran-3-carboxamide,

there is obtained

a. 2-(p-chlorophenyl)-6-phenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide,

b. 2-(p-fluorophenyl)-6-phenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide,

c. 2-(p-tolyl)-6-phenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide,

d. 2-(p-anisyl)-6-phenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide,

e. 2-ethyl-6-phenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide,

f. 2-phenyl-6-(p-chlorophenyl)-N-methyl-4-oxo-4H-pyran-3-carboxamide,

g. 2-phenyl-6-(p-fluorophenyl)-N-methyl-4-oxo-4H-pyran-3-carboxamide,

h. 2-phenyl-6-(p-tolyl)-N-methyl-4-oxo-4H-pyran-3-carboxamide,

i. 2-phenyl-6-(p-anisyl)-N-methyl-4-oxo-4H-pyran-3-carboxamide,

j. 2-phenyl-6-(t-butyl)-N-methyl-4-oxo-4H-pyran-3-carboxamide, or

k. 2-ethyl-6-(t-butyl)-N-methyl-4-oxo-4H-pyran-3-carboxamide,respectively.

What is claimed is:
 1. A compound of the formula ##STR8## where R₁ andR₂ representwhere ##STR9## R₄ is hydrogen, halogen having an atomicweight of from 19 to 36, lower alkoxy or lower alkyl; and R₃ is loweralkyl.
 2. The compound of claim 1, which is2,6-diphenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide.
 3. A compound of theformula ##STR10## where R₁ and R₂ each independently is lower alkyl or##STR11## where R₄ is hydrogen, halogen having an atomic weight of from19 to 36, lower alkoxy or lower alkyl; andR₃ is lower alkyl.
 4. Thecompound of claim 3, which is5,6-dihydro-2,6-diphenyl-N-methyl-4-oxo-4H-pyran-3-carboxamide.